PROJECT SUMMARY/ABSTRACT Presurgical fMRI is increasingly performed in large medical centers across the US and in the world, including here at Johns Hopkins. It is commonly used in brain tumor and epilepsy patients to noninvasively locate essential cortical sensorimotor and language areas and to determine the language dominant hemisphere prior to surgery, thus helping to reduce the need for invasive diagnostic procedures such as intraoperative cortical stimulation mapping. However, a significant subpopulation of patients undergoing presurgical fMRI are affected by the well-known problems of geometric distortion and signal dropout (thus compromised sensitivity) in regions with large magnetic susceptibility effects when using the current standard BOLD fMRI method: gradient echo (GRE) echo-planar-imaging (EPI). These include several frontal and temporal regions particularly relevant for language mapping in presurgical fMRI. Furthermore, such susceptibility artifacts can also arise from cavities related to previous surgery, calcified structures, hemorrhage, and metal implants. For instance, about 25% of our presurgical fMRI referrals have undergone prior resection and are being considered for a second resection, who will suffer from susceptibility artifacts related to resection cavities and surgical metallic craniotomy hardware. Although many methods have been developed to mitigate these problems, most are region dependent or require extra data acquisition. We have recently developed a T2-prepared (T2prep) BOLD fMRI method, which showed minimal distortion and dropout and sufficient BOLD sensitivity in the entire brain even in the presence of metallic head implants, and superior BOLD sensitivity than GRE EPI in regions affected by large susceptibility artifacts. The method was initially developed at ultra-high magnetic field (7 Tesla, 7T). The goal of this R21 is to optimize and validate T2prep BOLD for presurgical fMRI in tumor patients on 3T clinical MRI scanners. Aim 1: To optimize whole-brain T2prep BOLD fMRI for typical presurgical fMRI paradigms in healthy volunteers on 3T clinical MRI scanners. The multiband techniques will be implemented for T2prep BOLD. Image quality, functional sensitivity and specificity (in regions with small or large susceptibility effects) will be compared with GRE EPI BOLD fMRI (current standard). Aim 2: To determine whether T2prep BOLD fMRI can be used as a complementary method for presurgical planning in brain tumor patients with large susceptibility artifacts at 3T. Functional results from patients using typical presurgical fMRI paradigms will be compared between T2prep BOLD and GRE EPI BOLD fMRI, and will be validated by intraoperative cortical stimulation mapping data. If the proposed research is successful, it is expected to benefit a significant subset of patients undergoing presurgical fMRI. As presurgical fMRI protocols often consist of several functional scans, T2prep BOLD fMRI can be feasibly incorporated into existing clinical protocols. Besides, we also expect the T2prep BOLD approach to be useful for other functional studies in neuroscience and clinical research as an alternative fMRI tool that can assess brain functions in previously less explored brain territories due to susceptibility related signal losses in EPI BOLD fMRI.